Mechanical regulation of endocytosis by protein condensate capillary forces

Max Ferrin, Postdoctoral Researcher

Background and Motivation

Endocytosis internalizes membrane cargo into vesicles

(Kaksonen and Roux, 2018)

Endocytosis internalizes membrane cargo into vesicles

(Kaksonen and Roux, 2018)

How do capillary forces of a protein droplet influence endocytic membrane bending?

How do capillary forces of a protein droplet influence endocytic membrane bending?

How do capillary forces of a protein droplet influence endocytic membrane bending?

Modeling endocytosis with droplet

Geometrical model of endocytosis mechanical energy

Geometrical model of endocytosis mechanical energy

Geometrical model of endocytosis mechanical energy

Geometrical model of endocytosis mechanical energy

Geometrical model of endocytosis mechanical energy

Geometrical model of endocytosis mechanical energy

Geometrical model of endocytosis mechanical energy

Visualization of geometrical model reaction coordinate h

How does the droplet regulate invagination?

1: Droplet can provide net assistive force to endocytosis

1: Droplet can provide net assistive force to endocytosis

1: Droplet can provide net assistive force to endocytosis

2: Droplet drives late invagination to completion

2: Droplet drives late invagination to completion

2: Droplet drives late invagination to completion

3: Droplet produces early invagination energy barrier

3: Droplet produces early invagination energy barrier

3: Droplet produces early invagination energy barrier

3: Droplet produces early invagination energy barrier

4: Droplet volume controls energy barrier magnitude

4: Droplet volume controls energy barrier magnitude

4: Droplet volume controls energy barrier magnitude

4: Droplet volume controls energy barrier magnitude

Proposed mechanical role of condensate in endocytosis

Outlook

Validation of geometrical model results with continuum mechanics model

Geometrical model Continuum mechanics model

Endocytosis is qualitatively different from other examples of droplet-mediated membrane bending

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(Kusumaatmaja et al., 2021; Lu et al., 2022)

Acknowledgments

z inkscape:window-width="1440" inkscape:window-height="847" inkscape:window-x="1665" inkscape:window-y="131" inkscape:window-maximized="1" inkscape:current-layer="svg8" />David DrubinNikhil KulkarniVinu HariharTyler HarmonFrank Jülicher

Proposed mechanical role of condensate in endocytosis